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Large gaps exist in understanding the symptomatic and functional impact of sarcoidosis, a rare multisystem granulomatous disease affecting fewer than 200,000 individuals in the United States. Smartphones could be used for prospective research, especially for rare diseases where organizing large cohorts can be challenging, given their near ubiquitous ownership and ability to track objective and subjective data with increasingly sophisticated technology.
We aimed to investigate whether smartphones could assess the quality of life (QoL) and physical activity of a large cohort of individuals with sarcoidosis.
We developed a mobile app (Sarcoidosis App) for a prospective, cross-sectional study on individuals with sarcoidosis. The Sarcoidosis App was made available on both Apple and Android smartphones. Individuals with sarcoidosis were recruited, consented, and enrolled entirely within the app. Surveys on sarcoidosis history, medical history, and medications were administered. Patients completed modules from the Sarcoidosis Assessment Tool, a validated patient-reported outcomes assessment of physical activity, fatigue, pain, skin symptoms, sleep, and lungs symptoms. Physical activity measured by smartphones was tracked as available.
From April 2018 to May 2020, the App was downloaded 2558 times, and 629 individuals enrolled (404, 64.2% female; mean age 51 years; 513, 81.6% White; 86, 13.7% Black). Two-thirds of participants had a college or graduate degree, and more than half of them reported an income greater than US $60,000. Both QoL related to physical activity (
We demonstrate that smartphones can prospectively recruit, consent, and study physical activity, QoL, and medication usage in a large sarcoidosis cohort, using both passively collected objective data and qualitative surveys that did not require any in-person encounters. Our study’s limitations include the study population being weighted toward more educated and wealthier individuals, suggesting that recruitment was not representative of the full spectrum of patients with sarcoidosis in the United States. Our study provides a model for future smartphone-enabled clinical research for rare diseases and highlights key technical challenges that future research teams interested in smartphone-based research for rare diseases should anticipate.
Sarcoidosis is a multisystem granulomatous disease that most commonly affects the lungs, skin, eyes, and lymph nodes. In the United States, over 185,000 patients with sarcoidosis seek medical care annually, and 25,000 new cases of sarcoidosis are diagnosed [
Sarcoidosis is a rare disease, which is defined as affecting fewer than 200,000 individuals. Clinical research of rare diseases is challenging—nearly one-third of rare disease clinical trials are discontinued with insufficient patient accrual being the most common reason [
The goal of our study was to develop and launch a smartphone app to assess patient-reported quality of life (QoL) in a large population of patients with sarcoidosis and to characterize patients’ symptomatology and functional status. We designed this app to describe physical activity and correlate physical activity data with self-reported characteristics through QoL surveys, medication use, and adverse effects and comorbidities. Here, we describe the development and launch of the app and present results from the surveys and physical activity data collected from patients.
The Sarcoidosis App [
Screenshots of new participant experience in the Sarcoidosis App (Android version).
Patients with sarcoidosis were recruited via outpatient dermatology clinic visits at the University of Pennsylvania Health System, the Foundation for Sarcoidosis Research mailing list, and targeted social media advertisements. After prospective participants downloaded the app, they were presented with an inclusion and exclusion criteria questionnaire to provide multiple means of participant recruitment. Participants were eligible for study enrollment if they were aged greater than 18 years, lived in the United States, and self-reported a diagnosis of sarcoidosis. Participants were asked for permission to enable the app to read HealthKit or Google Fit data. To ensure participants understood the risks, benefits, and options of study participation, they were required to pass a quiz concerning these issues before digitally signing the informed consent document (
The Sarcoidosis App administered baseline surveys of (1) sarcoidosis history, (2) pertinent medical history, (3) sarcoidosis treatment medications, and (4) items from modules of the Sarcoidosis Assessment Tool (SAT). The SAT is a validated patient-reported assessment that comprises select generic measures from the Patient-Reported Outcomes Measurement Information System, as well as several sarcoidosis-specific item banks, including physical functioning, satisfaction with roles and activities, fatigue, pain interference, sleep disturbance, lung concerns, skin concerns, and skin stigma and embarrassment [
Descriptive statistics were calculated for demographic information, patient-reported outcomes, and physical activity data. Missing data were excluded from analyses except where described. Spearman correlation coefficients were calculated for correlating responses to the SAT modules for physical activity, lungs, and fatigue with average daily steps and traveled distance from smartphone-recorded data, as much of the survey and physical activity measures were not normally distributed. In addition, the use of ranks through Spearman correlation diminishes the influence of outliers in some of the physical activity measures. All statistics were calculated using Stata (version 16.1; StataCorp) and R (version 3.6.1; The R Foundation for Statistical Computing). The survey data and physical activity data used in this study is available upon reasonable request to BC and MR.
This study was approved by the institutional review board of the University of Pennsylvania (824080). This paper adheres to STROBE (Strengthening the Reporting of Observational studies in Epidemiology) reporting guidelines. Participants who met eligibility criteria proceeded to provide electronic informed consent.
From April 2018 to May 2020, the app was downloaded 2558 times: 1603 from the Apple App Store and 955 from Google Play. A quarter (629/2558) of downloads converted to study participation, with 629 unique participants completing at least one component of the background survey concerning basic demographic data (
Baseline characteristics of participants in the Sarcoidosis App study (N=629).
Characteristic | Value | |
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Female | 404 (64.2) |
|
Male | 199 (31.6) |
|
Missing | 26 (4.1) |
Mean age (years), mean (median; SD) | 51.0 (50; 10.95) | |
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White | 513 (81.6) |
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Black or African American | 86 (13.7) |
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Other/Unknown | 27 (4.3) |
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Missing | 3 (0.5) |
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Hispanic/Latino | 32 (5.1) |
|
Non-Hispanic | 587 (93.3) |
|
Missing | 10 (1.6) |
BMIa, mean (SD) | 32.12 (7.75) | |
|
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|
<1 | 127 (20.2) |
|
1-5 | 251 (39.9) |
|
5-20 | 197 (31.3) |
|
>20 | 52 (8.3) |
|
Missing | 2 (0.3) |
|
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|
High school | 8 (1.3) |
|
General Educational Development | 205 (32.6) |
|
College | 266 (42.3) |
|
Graduate | 150 (23.8) |
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Student | 6 (1.0) |
|
Part-time | 44 (7.0) |
|
Full-time | 316 (50.2) |
|
Unemployed | 61 (9.7) |
|
Disabled | 114 (18.1) |
|
Retired | 82 (13.0) |
|
Missing | 6 (1.0) |
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<15,000 | 49 (7.8) |
|
15,000-30,000 | 58 (9.2) |
|
30,000-60,000 | 139 (22.1) |
|
60,000-100,000 | 166 (26.4) |
|
>100,000 | 194 (30.8) |
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Missing | 23 (3.7) |
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No financial impact | 124 (19.7) |
|
Slightly affected | 223 (35.5) |
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Greatly affected | 178 (28.3) |
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Severely affected | 101 (16.1) |
|
Missing | 3 (0.5) |
aBMI was obtained from 605 participants.
In total, 597 unique participants filled out at least one of the SAT modules. The mean scores of each SAT module and their SDs are reported in
Sarcoidosis Assessment Test (SAT) survey results at baseline. A score of 50 represents the mean score of the original calibration sample of the SAT.
SAT module | Participants, n | Module score, mean (SD) |
Activity [+]a | 552 | 39.90 (7.97) |
Fatigue [–]b | 564 | 62.67 (9.32) |
Lungs [–] | 572 | 45.87 (8.46) |
Pain [–] | 544 | 60.48 (10.63) |
Skin symptoms [–] | 208 | 57.80 (6.99) |
Sleep [–] | 567 | 58.38 (9.51) |
Stigma/embarrassment/skin impact [–] | 535 | 49.73 (8.65) |
aA higher score representing a higher quality of life.
bA higher score representing a lower quality of life.
Where data were available for both SAT survey responses and device-measured physical activity, correlational analyses were performed. SAT physical activity scores positively correlated with average daily steps (n=226), and SAT fatigue scores negatively correlated with average daily steps (n=245) (
Correlation between Sarcoidosis Assessment Test surveys of physical activity, lung symptoms, and fatigue with device-reported physical activity data. [+] indicates that a higher score represents a higher quality of life. [-] indicates that a higher score represents a lower quality of life. P and ρ are the
Correlation between Sarcoidosis Assessment Test surveys of physical activity, lung symptoms, and fatigue with device-reported average daily distance traveled. [+] indicates that a higher score represents a higher quality of life. [-] indicates that a higher score represents a lower quality of life. P and ρ are the
Medical resource usage was assessed among 517 unique participants who completed at least one question of an initial survey (
Initial response to survey of medical resource usage (N=517).
Variables | Value, n (%) | |
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None | 206 (39.8) |
|
1 | 153 (29.6) |
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More than 1 | 156 (30.1) |
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||
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None | 392 (75.8) |
|
1 | 70 (13.5) |
|
More than 1 | 52 (10.1) |
|
||
|
None | 442 (85.5) |
|
1 | 57 (11.0) |
|
More than 1 | 18 (3.5) |
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||
|
None | 478 (94.5) |
|
1 | 31 (6.0) |
|
More than 1 | 7 (1.4) |
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None | 279 (54.0) |
|
1 day | 45 (8.7) |
|
2-6 days | 73 (14.1) |
|
7-14 days | 22 (4.3) |
|
>Half month | 12 (2.3) |
|
Entire month | 64 (12.4) |
aER: emergency room.
In total, 614 unique participants completed at least one question from the baseline medication survey (
Participants were also asked to complete a survey concerning medication adverse effects within the prior month (
Responses to survey of baseline medication usage (N=614).
Variables | Participants, n/N (%) | |
Are you currently being treated with medications for your sarcoidosis? (Yes) | 437/614 (71.2) | |
Are you taking prednisone for sarcoidosis? | 257/437 (41.9) | |
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1-10 | 131/257 (50.9) |
|
11-20 | 65/257 (25.3) |
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21-60 | 57/257 (22.2) |
|
>61 | 4/257 (1.6) |
Are you taking any medications other than prednisone for sarcoidosis? | 354/437 (57.7) | |
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Hydroxychloroquine | 71/354 (20.1) |
|
Methotrexate | 134/354 (37.9) |
|
Chloroquine | 4/354 (1.1) |
|
Azathioprine | 29/354 (8.2) |
|
Leflunomide | 6/354 (1.7) |
|
Mycophenolate mofetil | 33/354 (9.3) |
|
Infliximab | 51/354 (14.4) |
|
Adalimumab | 28/354 (7.9) |
|
Other medications | 182/354 (51.4) |
Medication adverse effects survey (N=526).
Variables | Participants, n/N (%) | |
Have you taken any medications for sarcoidosis in the past month? | 379/526 (72.1) | |
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Yes, major side effects requiring change in medications | 104/379 (27.4) |
|
Yes, minor side effects | 140/379 (36.9) |
|
Possibly/unsure | 78/379 (20.6) |
|
No | 70/379 (18.5) |
In this study, we demonstrate the novel use of smartphones to prospectively recruit, consent, and study physical activity and QoL in a large cohort of individuals with sarcoidosis, using both objective health tracking data and qualitative survey responses. We were able to demonstrate a strong correlation between the assessment of physical state and the activity level of participants with sarcoidosis, measured by smartphone apps. Specifically, participants who were more active, as measured by daily steps and distance traveled as tracked by their smartphones, also had physical activity and fatigue scores, representing a smaller impact of their disease on these domains on the SAT—a previously-defined patient-reported QoL metric [
The findings of this study suggest that smartphone technology may have advantages in the conduct of prospective clinical research in sarcoidosis and other rare diseases, though robust human and technical resources are critical. First, these data suggest smartphones have potential to enroll patients with sarcoidosis in clinical trials and reliably assess them without requiring a traditional in-person clinic visit. In this way, the clinical research study can be brought directly to participants, bypassing financial and geographic barriers of many socially disadvantaged patients with sarcoidosis, who are often unrepresented in clinical trials. However, these methods cannot replace studies that require laboratory testing or imaging. Second, as these assessments can be made in real time without investigator prompting, this method may avoid significant recall bias and investigator influence respectively. Third, the capability of integrating objective health tracking data with subjective survey data offers a multidimensional assessment of patients with sarcoidosis. In this way, studies using smartphones could provide alternative channels of demonstrating construct validity of patient-reported outcomes.
The strengths of our study were tempered by the technical challenges of developing and maintaining a mobile app. Clinical research teams without strong technical experience will encounter many obstacles in designing and launching mobile apps, and partnerships with technology companies are essential to the success of these projects. However, lack of cross-disciplinary understanding presents substantial challenges to meaningful collaboration with external stakeholders; clinical research teams may not even be able to envision what is technically possible, and developers may lack perspective on how these products are actually delivered to patients [
There were several limitations regarding the background of participants. First, individuals self-reported a diagnosis of sarcoidosis, which introduces the possibility of participants without a true diagnosis, even though participants were recruited directly from sarcoidosis clinics and advocacy groups for patients with sarcoidosis. Another limitation of our study is that our study population was weighted toward more educated and wealthier individuals. It is possible that the rate of response and familiarity with smartphone apps in our cohort was not representative of the full population of patients with sarcoidosis in the United States, particularly older individuals and those with low technology literacy. Future mobile app studies of sarcoidosis and other rare diseases should prioritize recruiting from a diverse set of sarcoidosis clinics that would provide a more representative sample, in addition to patient advocacy groups. Given that sarcoidosis results in disparate outcomes by race, sex, and socioeconomic class [
Future apps could also integrate environmental data, such as location, weather, and air quality to provide additional dimensions of analysis. Wearable devices, such as smartwatches, can also provide valuable data, though ownership is not as prevalent. Beyond observational research, smartphones also present opportunities for digital therapeutics, which are evidence-based interventions driven by software. For example, one group has demonstrated that a smartphone-based stress management tool significantly reduced stress and fatigue in patients with sarcoidosis compared to control patients [
Consent quiz to ensure participants understood the risks, benefits, and options of study participation.
quality of life
Sarcoidosis Assessment Test
Strengthening the Reporting of Observational studies in Epidemiology
We acknowledge Kathleen Chen, the University of Pennsylvania Patient Centered Outcomes Research pilot grant, Siegel Family philanthropic support, the Foundation for Sarcoidosis Research, Medable (Stephanie Adamkiewicz), and the Department of Dermatology Clinical Studies Unit.
DMO and MR developed the Sarcoidosis App with advice from MJ. BC, DMO, and MW performed statistical analyses. HS and IB provided statistical advice. BC and DMO acted as cofirst authors for the manuscript. All authors contributed to the drafting, editing, and submission of the manuscript, led by BC, DMO, MR, and MJ. BC and MR take responsibility for the content of the manuscript, including the data and analysis.
None declared.